Descemet Endothelial Thickness Comparison Trial

NCT ID: NCT02373137

Last Updated: 2020-11-25

Study Results

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Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-22

Study Completion Date

2023-05-30

Brief Summary

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The purpose of this study is to compare visual acuity outcomes of two types of endothelial keratoplasty: 1) Ultrathin Descemet's Stripping Endothelial Keratoplasty (DSAEK) or 2) Descemet's Membrane Endothelial Keratoplasty (DMEK). Half of the participants will be randomized to have DSAEK and the other half will have DMEK.

Detailed Description

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Corneal transplantation has evolved rapidly in recent years. Lamellar keratoplasty to replace diseased endothelium has led to faster recovery times, fewer complications, and better visual acuity outcomes. Currently, Descemet's Stripping Endothelial Keratoplasty (DSAEK) is the most common procedure because of its relative ease and good outcomes. Newer techniques such as Descemet's Membrane Endothelial Keratoplasty (DMEK), where Descemet's membrane alone is transplanted, has the potential to further improve visual acuity outcomes, produce fewer higher-order corneal aberrations and decrease rejection rates. However, donor preparation, increased intra-operative times, and problems with donor attachment in DMEK are all important limitations.

There are three potential mechanisms by which DMEK may provide better visual acuity outcomes than DSAEK; graft thickness, interface haze and corneal higher-order aberrations. Graft thickness has been correlated with best spectacle corrected visual acuity (BSCVA) outcomes among thinner grafts. One retrospective case series found that 71% of thin endothelial grafts (defined as \<131μm) had BSCVA of 20/25 or better while only 50% of thick grafts (defined as ≥131) achieved this. In addition, higher-order aberrations, in particular of the posterior cornea, are increased after DSAEK. Theoretically, given the decreased tissue transplanted after DMEK this would be lessened, however, one retrospective series looking at higher order aberrations in DMEK compared with DSAEK found no difference in posterior aberrations of the central 4.0 mm zone between the two groups. Finally, interface haze may be increased in DSAEK and has been correlated with BSCVA.

Ultrathin DSAEK involves donor preparation with a deep microkeratome pass to produce donor grafts less than 100 um thick. This procedure may have similar results to DMEK but without the technical difficulties. Several large prospective series show similar visual outcome results and rates of immunologic rejection between ultrathin DSAEK and DMEK, however comparisons are difficult. This comparative effectiveness clinical trial could directly address these important issues. The investigators also anticipate that secondary analyses of the trial data will allow us to address several more.

Conditions

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Keratoplasty Grafting, Corneal Transplantation, Corneal Transplantation, Cornea Keratoplasty, Lamellar

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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DSAEK

Type of corneal transplant; Tissue grafts will be cut to the right thickness using a microkeratome prepared at the eye bank per standard eye bank protocol (about 60-90 microns thick). A 4 mm corneal incision will be used, with Endoserter as the means of inserting the graft, an FDA approved device for this purpose.

Group Type OTHER

DSAEK

Intervention Type PROCEDURE

Endoserter

Intervention Type DEVICE

The Endoserter, a corneal endothelium device, is an approved FDA device. This will be used to insert and position the graft into the anterior chamber during endothelial replacement surgery. It is a sterile, single-use instrument.

Prednisolone

Intervention Type DRUG

Prednisolone is a corticosteroid used to alleviate swelling post-surgery.

Ofloxacin

Intervention Type DRUG

Ofloxacin is an antibiotic used to treat bacterial infections of the eye.

Tropicamide

Intervention Type DRUG

Tropicamide is a prescription drug used to dilate pupils during an eye exam.

Phenylephrine

Intervention Type DRUG

Phenylephrine is a prescription drug used to dilate pupils during an eye exam.

DMEK

Type of corneal transplant; Endothelial grafts will be pre-peeled at the eyebank (70%). In the operating room the remaining 30% will be peeled, and the endothelium will be stained with trypan blue. A 3.5 mm corneal incision will be used and the graft will be inserted with a modified jones tube injector. The tap technique will be used to position the graft.

Group Type OTHER

DMEK

Intervention Type PROCEDURE

Prednisolone

Intervention Type DRUG

Prednisolone is a corticosteroid used to alleviate swelling post-surgery.

Ofloxacin

Intervention Type DRUG

Ofloxacin is an antibiotic used to treat bacterial infections of the eye.

Tropicamide

Intervention Type DRUG

Tropicamide is a prescription drug used to dilate pupils during an eye exam.

Phenylephrine

Intervention Type DRUG

Phenylephrine is a prescription drug used to dilate pupils during an eye exam.

Jones Tube

Intervention Type DEVICE

The Jones Tube will be used to insert the graft into a 3.5 mm corneal incision during endothelial replacement surgery.

Interventions

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DSAEK

Intervention Type PROCEDURE

DMEK

Intervention Type PROCEDURE

Endoserter

The Endoserter, a corneal endothelium device, is an approved FDA device. This will be used to insert and position the graft into the anterior chamber during endothelial replacement surgery. It is a sterile, single-use instrument.

Intervention Type DEVICE

Prednisolone

Prednisolone is a corticosteroid used to alleviate swelling post-surgery.

Intervention Type DRUG

Ofloxacin

Ofloxacin is an antibiotic used to treat bacterial infections of the eye.

Intervention Type DRUG

Tropicamide

Tropicamide is a prescription drug used to dilate pupils during an eye exam.

Intervention Type DRUG

Phenylephrine

Phenylephrine is a prescription drug used to dilate pupils during an eye exam.

Intervention Type DRUG

Jones Tube

The Jones Tube will be used to insert the graft into a 3.5 mm corneal incision during endothelial replacement surgery.

Intervention Type DEVICE

Other Intervention Names

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Millipred Orapred Omnipred Econopred Flo-Pred Ocuflox Floxin Mydriacyl

Eligibility Criteria

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Inclusion Criteria

* Damaged or diseased endothelium from Fuchs or Pseudophakic Bullous Keratopathy
* Good candidates for corneal transplantation for either DMEK or DSAEK
* Willingness and ability to undergo a cornea transplantation
* Willingness to participate in follow-up visits

Exclusion Criteria

* Participants who are decisionally and/or cognitively impaired
* Participants who are not suitable for the DMEK or DSAEK surgeries
* Prior Endothelial Keratoplasty (EK) or any other ophthalmic surgery except uncomplicated cataract surgery
* Indication for surgery that is not suitable for EK (e.g. keratoconus, stromal dystrophies and scars)
* Presence of a condition that increases the probability for failure (e.g., heavily vascularized cornea, uncontrolled uveitis)
* Other primary endothelial dysfunction conditions including posterior polymorphous corneal dystrophy and congenital hereditary corneal dystrophy
* Aphakia, or anterior chamber intraocular lens (IOL) in study eye prior to or anticipated during EK
* Planned intraocular lens exchange of an anterior chamber IOL with a posterior chamber IOL in study at time of study EK
* Pre-operative central sub-epithelial or stromal scarring that the investigator believes is visually significant and could impact post-operative stromal clarity assessment
* Peripheral anterior synechiae (iris to angle) in the angle greater than a total of three clock hours
* Hypotony (Intraocular pressure \<10mmHg)
* Uncontrolled (defined as intraocular pressure \>25mmHg) glaucoma Visually significant optic nerve or macular pathology
* Visually significant optic nerve or macular pathology
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, San Francisco

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role lead

Responsible Party

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Winston Chamberlain, MD, PhD

Ophthalmologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Winston Chamberlain, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Jennifer Rose-Nussbaumer, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Charles Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Byers Eye Institute, Stanford University

Palo Alto, California, United States

Site Status

F. I. Proctor Foundation, University of California, San Francisco

San Francisco, California, United States

Site Status

Casey Eye Institute, Oregon Health & Science University

Portland, Oregon, United States

Site Status

Countries

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United States

References

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Price FW Jr, Price MO. Evolution of endothelial keratoplasty. Cornea. 2013 Nov;32 Suppl 1:S28-32. doi: 10.1097/ICO.0b013e3182a0a307.

Reference Type BACKGROUND
PMID: 24104929 (View on PubMed)

Chen ES, Terry MA, Shamie N, Hoar KL, Friend DJ. Descemet-stripping automated endothelial keratoplasty: six-month results in a prospective study of 100 eyes. Cornea. 2008 Jun;27(5):514-20. doi: 10.1097/ICO.0b013e3181611c50.

Reference Type BACKGROUND
PMID: 18520497 (View on PubMed)

Ham L, Dapena I, van Luijk C, van der Wees J, Melles GR. Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy: review of the first 50 consecutive cases. Eye (Lond). 2009 Oct;23(10):1990-8. doi: 10.1038/eye.2008.393. Epub 2009 Jan 30.

Reference Type BACKGROUND
PMID: 19182768 (View on PubMed)

Dirisamer M, van Dijk K, Dapena I, Ham L, Oganes O, Frank LE, Melles GR. Prevention and management of graft detachment in descemet membrane endothelial keratoplasty. Arch Ophthalmol. 2012 Mar;130(3):280-91. doi: 10.1001/archophthalmol.2011.343. Epub 2011 Nov 14.

Reference Type BACKGROUND
PMID: 22084160 (View on PubMed)

Kruse FE, Laaser K, Cursiefen C, Heindl LM, Schlotzer-Schrehardt U, Riss S, Bachmann BO. A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty. Cornea. 2011 May;30(5):580-7. doi: 10.1097/ico.0b013e3182000e2e.

Reference Type BACKGROUND
PMID: 21598430 (View on PubMed)

Rudolph M, Laaser K, Bachmann BO, Cursiefen C, Epstein D, Kruse FE. Corneal higher-order aberrations after Descemet's membrane endothelial keratoplasty. Ophthalmology. 2012 Mar;119(3):528-35. doi: 10.1016/j.ophtha.2011.08.034. Epub 2011 Dec 22.

Reference Type BACKGROUND
PMID: 22197439 (View on PubMed)

Busin M, Madi S, Santorum P, Scorcia V, Beltz J. Ultrathin descemet's stripping automated endothelial keratoplasty with the microkeratome double-pass technique: two-year outcomes. Ophthalmology. 2013 Jun;120(6):1186-94. doi: 10.1016/j.ophtha.2012.11.030. Epub 2013 Mar 1.

Reference Type BACKGROUND
PMID: 23466268 (View on PubMed)

Guerra FP, Anshu A, Price MO, Giebel AW, Price FW. Descemet's membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss. Ophthalmology. 2011 Dec;118(12):2368-73. doi: 10.1016/j.ophtha.2011.06.002. Epub 2011 Aug 27.

Reference Type BACKGROUND
PMID: 21872938 (View on PubMed)

Ang MJ, Chamberlain W, Lin CC, Pickel J, Austin A, Rose-Nussbaumer J. Effect of Unilateral Endothelial Keratoplasty on Vision-Related Quality-of-Life Outcomes in the Descemet Endothelial Thickness Comparison Trial (DETECT): A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2019 Jul 1;137(7):747-754. doi: 10.1001/jamaophthalmol.2019.0877.

Reference Type DERIVED
PMID: 31046075 (View on PubMed)

Chamberlain W, Lin CC, Austin A, Schubach N, Clover J, McLeod SD, Porco TC, Lietman TM, Rose-Nussbaumer J. Descemet Endothelial Thickness Comparison Trial: A Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty. Ophthalmology. 2019 Jan;126(1):19-26. doi: 10.1016/j.ophtha.2018.05.019. Epub 2018 Jun 23.

Reference Type DERIVED
PMID: 29945801 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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IRB00010818

Identifier Type: -

Identifier Source: org_study_id